The proposed research will (1) define the action of volatile anesthetics (halothane, enflurane and diethyl ether) on the cyclic 3',5'-adenosine monophosphate (cAMP) system of myocardium, (2) identify the sites of action and characterize the mechanism by which these anesthetics act on the enzymes of the cAMP system: adenylate cyclase, cAMP-phosphodiesterase and protein kinase, and (3) identify the pharmacological effects of these anesthetics which are mediated by cAMP in heart. To achieve these goals, changes in enzyme activity, cAMP content, receptor characteristics caused by anesthetics, and the interaction of anesthetics controlling cardiac function will be determined. This study will establish to what extent the effects of these anesthetics on the heart (mainly cardiac depression and decrease of the positive inotropic effect of catecholamines) are related to their effects on the cAMP system. Rat, cat, guinea pig and dog heart and cat right ventricular papillary muscle will be used for in vitro biochemical and functional studies, respectively. The effects of anesthetics, at increasing concentrations, on adenylate cyclase, phosphodiesterase and protein kinase will be determined in tissue homogenates by the methods of Krishna, Thompson-Appleman and Miayamoto, respectively. The effects of anesthetics on cAMP content in intact tissue and receptor characteristics in a membrane preparation will be determined according to Gilman and Alexander et al, respectively. Protein content will be measured by the procedure of Lowry.